He traveled throughout West Asia and France in his youth, and after some medical training and a year of practice in his native Aleppo, during which he wrote several works, he enrolled in a medical school in Paris; yet, declining health and growing blindness forced him to return to Aleppo, where he produced more literary works until his early death.

Marrash adhered to the principles of the French Revolution and defended them in his own works, implicitly criticizing Ottoman rule in West Asia and North Africa.

[7] Having earned wealth and standing in the 18th century, the family was well established in Aleppo,[8] although they had gone through troubles: a relative of Francis, Butrus Marrash, was killed by the wali's troops in the midst of a Catholic–Orthodox clash in April 1818.

[12] He had built up a large private library[13] to give his three children Francis, Abdallah and Maryana a thorough education, particularly in the field of Arabic language and literature.

[17][d] In 1853, Francis accompanied his father once again, on a business trip of several months to Beirut, where there was a noticeable presence and cultural influence of Europeans.

[21] Marrash practiced medicine for about a year;[15] however, deeming it safer for his trade to become a state-licensed physician, he went to Paris in 1866 so as to continue his medical education at a school.

[26] In this work, Marrash expressed ideas of political and social reforms,[f] highlighting the need of the Arabs for two things above all: modern schools and patriotism "free from religious considerations".

But the significance of this work also lay in Marrash's attempt to blend European thought with his own reading of the Christian belief in universal love.

[45] He also wrote many articles in the popular press;[46] in those published in Butrus al-Bustani's journal Al-Jinan, he showed himself favourable to women's education, which he restricted however to reading, writing, and a little bit of arithmetic, geography and grammar.

[6] Writings published in periodicals: Mention no longer the driver on his night journey and the wide striding camels, and give up talk of morning dew and ruins.

[53] Shmuel Moreh has also considered some passages from Ghabat al-haqq and Rihlat Baris to be prose poetry, while Salma Khadra Jayyusi has described his prosaic writing as "often Romantic in tone, rising sometimes to poetic heights, declamatory, vivid, colourful and musical", calling it the first example of poetic prose in modern Arabic literature.

[60] According to Shmuel Moreh, Gibran's own works echo Marrash's style and "many of [his] ideas on enslavement, education, women's liberation, truth, the natural goodness of man, and the corrupted morals of society".

[62] Moreover, Khalil Hawi has stated that many of Marrash's recurring expressions became stock images for Arab writers of the 20th century: he has mentioned, for example, "the valleys of mental contemplation", "the wings of thoughts", "solicitudes and dreams", "the veils of history", "the Kingdom of the Spirit", "the nymphs of the forest, the spring and the dawn", "golden diadems", "the jewels of light", "the storms of days and nights", and "the smoke of revenge and the mist of anger".